Overexpression of the reg gene in non-obese diabetic mouse pancreas duringactive diabetogenesis is restricted to exocrine tissue

We demonstrated pancreatic reg gene overexpression in non-obese diabetic (N OD) mice during active diabetogenesis. The aim of this study was to determi ne in which part of the pancreas (endocrine and/or exocrine) the gene(s) an d the protein(s) were expressed and if their localization changed with prog ression of the disease. In situ hybridization analysis and immunocytochemic al studies were carried out on pancreas of female and male NOD mice. Both d evelop insulitis but diabetes develops only in females and in males only wh en treated by cyclophosphamide. Our results show that whatever the age, sex , and presence of insulitis and/or diabetes, the expression of reg mRNAs an d of the corresponding protein(s) was restricted to exocrine tissue. Moreov er, reg remains localized in acinar cells in the two opposite situations of (a) cyclophosphamide-treated males in a prediabetic reg gene stage present ing a high level of both insulin and reg mRNAs, and (b) the overtly diabeti c reg protein females with no insulin but a high level of reg mRNA. These f indings suggest that overexpression of the reg gene(s) might represent a de fense of the acinar cell against pancreatic localization aggression.